The potential role of immunotherapy is reawakened with the conclusive demonstration of anti-tumor immune response in an autochthonous tumor-host. First, the central problem in immunotherapy is not to make a tumor host immune to his tumor; but rather to make the existing host's anti-tumor effector mechanisms more effective. Second, the practical problems of immunological intervention are more complex due to poor understanding of tumor-host relationship. Third, the animal tumor model being studied does not reflect situations in humans. The objective of this proposal is to investigate: a) the way in which cell-mediated and humoral responses to TRA (Tumor Rejection Antigens) demonstrable in vitro relate to tumor status in vivo in a chemically induced colo-rectal tumor-rat model. An animal tumor model which possibly reflects situations in humans bearing colon carcinoma; and b) a basis for immuno- therapy trials in colo-rectal tumors in rat model, by studying the effects of combined immune manipulation by non- specific immune potentiators and specific unblocking therapy both on anti-tumor immune responses in vitro and tumor status in vivo. We will use an in vitro technique based on target cell-effector cell interaction, i.e., microcytotoxicity test, to analyze the changes in anti-tumor immune response. The in vitro responses will be correlated with the in vivo status of tumor during specific anti-tumor immune manipulation. In addition to the microcytotoxicity test for the detection of cell-mediated immune response, macrophage migration inhibition test (MMI) will also be used (only in a few selected cases) and the results obtained by MMI test will be correlated with those of the microcytotoxicity test.